Genome of mouse ES cells is organized as nucleosome wrapping domains
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE243091 | GEO | 2024/10/28
REPOSITORIES: GEO
Similar Datasets
Project description:The genomic positions of nucleosomes are a defining feature of the epigenomic state and hence of cell identity. Signal-dependent transcription factors (SDTFs), upon activation, modify the positioning of nucleosomes and cause epigenome remodeling. Here, we developed Markov models of nucleosome wrapping and unwrapping, and fit them to high resolution deep sequencing data of DNA accessibility to reveal biophysical principles of nucleosome dynamics. We found that 1) the dynamics of DNA unwrapping are significantly slower in vivo than reported from in vitro experimental data, 2) there is clear evidence for cooperativity in wrapping and unwrapping, 3) SDTF activity produced highest eviction probability when its binding site is close to but not on top of the nucleosome dyad, and 4) oscillatory SDTFs produce more variability than constant SDTF activities. Our work uncovers the regulatory rules governing nucleosome dynamics in vivo, which can predict epigenomic alterations during inflammation at single nucleosome resolution.
2022-04-24 | GSE156385 | GEO
Project description:Nucleosome is the basic structural unit of chromatin, and its dynamics plays critical roles in the regulation of genome functions. However, how the nucleosome structure is regulated by histone variants in vivo is still largely uncharacterized. Here, by employing Micrococcal nuclease (MNase) digestion of crosslinked chromatin followed by chromatin immunoprecipitation (ChIP) and paired-end sequencing (MNase-X-ChIP-seq), we mapped genome-wide unwrapping states of nucleosomes containing histone variant H2A.Z in mouse embryonic stem (ES) cells. We found that H2A.Z is enriched with unwrapped nucleosomes. Interestingly, the function of +1 H2A.Z nucleosome in transcriptional regulation is correlated with the unwrapping states. We further showed that H2A.Z nucleosomes adjacent the CTCF binding sites (CBS) may adopt an open conformation. We confirmed the unwrapping state of H2A.Z nucleosomes under native condition by re-ChIP of H2A.Z after CTCF CUT&RUN in mouse ES cells. Importantly, we found that depletion of H2A.Z results in increased CTCF binding, indicating dynamic competition between the unwrapped H2A.Z nucleosomal intermediates and CTCF at the CBS. Taken together, our results showed that histone variant H2A.Z regulates transcription and CTCF binding through modulating the nucleosome unwrapping.
2020-04-27 | GSE146082 | GEO
Project description:A key step towards defining the structure-function relationship of the genome is to identify the molecular mechanisms that drive higher-order genome folding. To this end, we reconstituted five S. cerevisiae chromosomes in vitro and developed a high-resolution MNase-based chromosome conformation capture assay to measure their 3D organization. We show that the formation of regularly spaced and phased nucleosome arrays is sufficient to drive higher-order genome folding into domains that resemble in vivo genome organization and thereby demonstrate that neither loop extrusion nor transcription are required for domain formation. The domain boundaries correspond to nucleosome-free regions and insulation strength scales with their width. Integrated molecular dynamics simulations show that domain compaction is dependent on nucleosome linker length, with longer linkers forming more compact structures. Together, our work demonstrates that fundamental properties of chromatin fibers are important determinants of higher-order genome folding and provides a proof-of-principle for bottom-up 3D genome studies.
2023-11-24 | GSE243340 | GEO
Project description:A key step towards defining the structure-function relationship of the genome is to identify the molecular mechanisms that drive higher-order genome folding. To this end, we reconstituted five S. cerevisiae chromosomes in vitro and developed a high-resolution MNase-based chromosome conformation capture assay to measure their 3D organization. We show that the formation of regularly spaced and phased nucleosome arrays is sufficient to drive higher-order genome folding into domains that resemble in vivo genome organization and thereby demonstrate that neither loop extrusion nor transcription are required for domain formation. The domain boundaries correspond to nucleosome-free regions and insulation strength scales with their width. Integrated molecular dynamics simulations show that domain compaction is dependent on nucleosome linker length, with longer linkers forming more compact structures. Together, our work demonstrates that fundamental properties of chromatin fibers are important determinants of higher-order genome folding and provides a proof-of-principle for bottom-up 3D genome studies.
2023-11-24 | GSE220645 | GEO
Project description:A key step towards defining the structure-function relationship of the genome is to identify the molecular mechanisms that drive higher-order genome folding. To this end, we reconstituted five S. cerevisiae chromosomes in vitro and developed a high-resolution MNase-based chromosome conformation capture assay to measure their 3D organization. We show that the formation of regularly spaced and phased nucleosome arrays is sufficient to drive higher-order genome folding into domains that resemble in vivo genome organization and thereby demonstrate that neither loop extrusion nor transcription are required for domain formation. The domain boundaries correspond to nucleosome-free regions and insulation strength scales with their width. Integrated molecular dynamics simulations show that domain compaction is dependent on nucleosome linker length, with longer linkers forming more compact structures. Together, our work demonstrates that fundamental properties of chromatin fibers are important determinants of higher-order genome folding and provides a proof-of-principle for bottom-up 3D genome studies.
2023-11-24 | GSE220644 | GEO
Project description:Histone variant H2A.Z regulates nucleosome unwrapping and CTCF binding in mouse ES cells
| PRJNA609170 | ENA
Project description:Nucleosome organization determines chromatin state, which subsequently controls genes expression or silencing. Nucleosome remodeling occurs during somatic cell reprogramming, but it remains undetermined to what degree the re-established nucleosome organization resembles between induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs). Here, we generated genome-wide maps of nucleosomes in mouse ESCs and iPSCs reprogrammed from somatic cells belonging to three different germ layers using a secondary reprogramming system. Pairwise comparisons show that nucleosome organization is nearly identical between ESCs and iPSCs regardless of the iPSCs’ tissue of origin. A distinct nucleosome occupancy pattern was observed at silent transcriptional units. Transcription factor binding sites possess characteristic nucleosomal architecture such that their access is governed under rotational setting and translational setting accordingly. Gene expression profiles further reveal that the transcriptional programs are highly correlated between iPSCs and ESCs. These findings indicate that nucleosome organizations can be accurately remodeled during nuclear reprogramming. Gene expression profiles of 5 cell lines with or without biological replicates
2014-12-09 | E-GEOD-46716 | biostudies-arrayexpress
Project description:Chromatin accessibility is a hallmark of active transcription and requires ATP-dependent nucleosome remodeling by Brahma-Associated Factor (BAF). However, the mechanistic link between transcription, nucleosome remodeling, and chromatin accessibility is unclear. Here, we used a chemical-genetic approach to dissect the interplay between RNA Polymerase II (RNAPII), BAF, and DNA-sequence-specific transcription factors (TFs) in mouse embryonic stem cells. By time-resolved chromatin profiling with acute transcription block at distinct stages, we show that RNAPII promoter-proximal pausing stabilizes BAF chromatin occupancy and enhances nucleosome eviction by BAF. We find that RNAPII and BAF probe both transcriptionally active and Polycomb-repressed genomic regions and provide evidence that TFs capture transient site exposure due to nucleosome unwrapping by BAF to confer locus specificity for persistent chromatin remodeling. Our study reveals the mechanistic basis of cell-type-specific chromatin accessibility. We propose a new paradigm for how functional synergy between dynamically acting chromatin factors regulates nucleosome organization.
2023-10-12 | GSE224292 | GEO
Project description:The organization of nucleosomes influences transcriptional activity by controlling accessibility of DNA binding proteins to the genome. Genome-wide nucleosome binding profiles have identified a canonical nucleosome organization at gene promoters, where arrays of well-positioned nucleosomes emanate from nucleosome-depleted regions. The mechanisms of formation and the function of canonical promoter nucleosome organization remain unclear. Here we analyze the genome-wide location of nucleosomes during zebrafish embryogenesis and show that well-positioned nucleosome arrays appear on thousands of promoters during the activation of the zygotic genome. The formation of canonical promoter nucleosome organization is independent of DNA sequence preference, transcriptional elongation, and robust RNA polymerase II (Pol II) binding. Instead, canonical promoter nucleosome organization correlates with the presence of Histone H3 Lysine 4 trimethylation (H3K4me3) and affects future transcriptional activation. These findings reveal that genome activation is central to the organization of nucleosome arrays during early embryogenesis.
2013-10-29 | GSE51766 | GEO
Project description:The organization of nucleosomes influences transcriptional activity by controlling accessibility of DNA binding proteins to the genome. Genome-wide nucleosome binding profiles have identified a canonical nucleosome organization at gene promoters, where arrays of well-positioned nucleosomes emanate from nucleosome-depleted regions. The mechanisms of formation and the function of canonical promoter nucleosome organization remain unclear. Here we analyze the genome-wide location of nucleosomes during zebrafish embryogenesis and show that well-positioned nucleosome arrays appear on thousands of promoters during the activation of the zygotic genome. The formation of canonical promoter nucleosome organization is independent of DNA sequence preference, transcriptional elongation, and robust RNA polymerase II (Pol II) binding. Instead, canonical promoter nucleosome organization correlates with the presence of Histone H3 Lysine 4 trimethylation (H3K4me3) and affects future transcriptional activation. These findings reveal that genome activation is central to the organization of nucleosome arrays during early embryogenesis.
2013-10-18 | GSE44269 | GEO